テモゾロミド 化学特性,用途語,生産方法
外観
白色～うすい褐色, 結晶性粉末～粉末
用途
アルキル化剤です。DNA 合成
阻害作用を示します。
用途
テモゾロミド（Temozolomide）は経口投与可能な抗がん剤である。商品名テモダール。アルキル化剤に属し、初発?再発の星状細胞腫（膠芽腫等）の悪性度の高い脳腫瘍の治療に用いられるほか、海外では悪性黒色腫の治療にも用いられる。 また承認外用法として乏突起神経膠腫の治療に、旧来の忍容性の低いPCV療法（プロカルバジン、ロムスチン、ビンクリスチン）の代わりに用いられている国もある。
効能
抗悪性腫瘍薬, アルキル化剤
商品名
テモダール (MSD); テモダール (MSD)
使用上の注意
不活性ガス封入
説明
Temozolomide was launched for the first time in the UK for the
treatment of patients with glioblastoma multiforme showing recurrence or
progression after standard therapy. It can be considered as a cyclic variant of
highly reactive triazenes producing a cascade of ionic or radical antitumoral
species. Temozolamide is a 3-methyl analog of mitozolomide and was shown to
be converted to cytotoxic triazene MCTIC. It can be prepared in 2 steps from 5-
aminoimidazole-4-carboxamide by diazotization then cyclization with
methylisocyanate. Mechanistically, the depletion of O6-alkylguanine-DNA
alkyltransferase (OGAT) in cells or tumors was shown to be correlated with the
cytotoxicity of temozolomide which is a potent inhibitor of this enzyme involved
in DNA repair activity.
Further approval applications for the treatment of other malignant gliomas such
as relapsed anaplastic astrocytoma, advanced metastatic melanoma were
submitted.
化学的特性
Off-white to light-pink crystalline solid, crystallized from dichloromethane, melting point 212℃ (decomposition). Maximum UV absorption (in 95% ethanol): 327nm.
使用
Temozolomide is an antineoplastic drug and an Imidazotetrazine alkylating agent. It induces apoptosis and causes cell cycle arrest at the G2/M checkpoint. It rapidly degrades in the body, producing the active metabolite MTIC, which exerts an anti-tumor effect. Moreover, temozolomide has shown effectiveness against paclitaxel-resistant tumors and has been utilized in the study of drug resistance mechanisms in glioblastoma cell lines.
製造方法
The synthesis of temozolomide involves several steps. First, 5-Amino-4-imidazolecarboxamide is diazotized using nitrite. Then, the diazotized compound is reacted with methyl isocyanate in dichloromethane. This reaction leads to the cyclization of the compound, ultimately resulting in the formation of temozolomide.
定義
ChEBI: An imidazotetrazine that is 3,4-dihydroimidazo[5,1-d][1,2,3,5]tetrazine which is substituted at positions 3, 4, and 8 by methyl, oxo, and carboxamide groups, respectively. A prodrug for MTIC (5-(3-methyltriaz-1-en-1-yl)-1H-i
idazole-4-carboxamide, formed by spontaneous hydrolysis of temozolomide in the body), it is used as an oral alkylating agent for the treatment of newly diagnosed malignant glioblastoma multiforme (concomitantly with radiotherapy) and malignant melanoma.
一般的な説明
Temozolomide can be called as an oral alkylating agent and antitumour drug, which may show potent activity in the treatment of recurrent gliomas or glioblastoma, a kind of tumour that affects the brain or spine.
生物活性
DNA methylating, chemotherapeutic agent. Displays antitumor activity against a board spectrum of tumors, including leukemias, lymphomas and solid tumors (IC 50 = 5.0 μ M for cytotoxicity against mouse TLX5 lymphoma cells).
臨床応用
This imidazolotetrazine derivative is administered orally in capsule form for the treatment of glioblastoma multiforme or in patients with anaplastic astrocytoma who have not responded to procarbazine or the nitrosoureas.
代謝
Oral absorption is rapid and complete. The CYP450 enzymes are not extensively involved in temozolomide metabolism, and less than 6% of the drug is excreted unchanged in the urine. Women clear the drug less effectively than men and have a higher incidence of severe neutropenia and thrombocytopenia in the initial therapy cycle. Food decreases temozolomide absorption, and myelosuppression is the most significant adverse effect.
テモゾロミド 上流と下流の製品情報
原材料
準備製品